Diabetic Peripheral Neuropathy Patients Research Articles

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy

Background/Aims: High glucose-induced oxidative stress and inflammatory responses play an important role in painful diabetic neuropathy by activating the TLR4/NFκB signal pathway. Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs provide a microenvironment favoring vascular regeneration but their low survival ratio in hyperglycemic conditions suppress the function to promote nerve growth. Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes remyelination after peripheral nerve injury. The aim of this study was to identify the role of Nrf2 in SC-mediated functional recovery after sciatic nerve injury. Methods: We compared plasma inflammatory factors in diabetic patients (DN) with/without diabetic peripheral neuropathy (DPN) and assessed whether Nrf2 expression in SCs could repair peripheral nerve injury in a rat model. Nrf2, TLR4/NFκB signal pathway and apoptosis relative protein expression were detected by western blot. Apoptosis and angiogenesis were determined by immunofluorescence and tubule formation assay, respectively. Regenerated nerves were determined by transmission electron microscope. Results: Higher levels of inflammatory factors and VEGF expression were found in DPN patients. Cellular experiments indicate that Nrf2 expression inhibits hyperglycemia-induced apoptosis and promotes angiogenesis by regulating the TLR4/NFκB signal pathway. Animal experiments show that nerve conduction velocity, myelin sheath thickness, and sciatic vasa nervorum are restored with transplantation of SCs overexpressing Nrf2. Conclusions: Taken together, the high survival ratio of SCs in a DPN rat model indicates that overexpression of Nrf2 restores nerve injury.

Evaluation and Comparison of Blood Parameters in Diabetic Patients with and without Peripheral Neuropathy

Introduction: Diabetic Peripheral Neuropathy (DPN) is the most prevalent and troublesome microvascular complication (50%) of Diabetes Mellitus (DM). The factors involved in the pathogenesis of diabetic neuropathy have not been understood completely. Studies have shown that neuronal dysfunction and inflammation play important roles in the development of DPN. Aim: To evaluate and compare the inflammatory marker Neutrophil to Lymphocyte Ratio (NLR) and serum markers calcium, urea, and uric acid in diabetic patients with and without peripheral neuropathy. Materials and Methods: We prospectively studied 118 diabetic patients who visited Kasturba Hospital, Manipal, Karnataka, India during December 2016- June 2017. After obtaining the ethical approval (IEC 791/2016), the patients were grouped into those with DPN (n=55) and without DPN (n=63). NLR and serum markers calcium, urea, and uric acid were estimated. Results: The data were analysed using Student's t-test and Mann-Whitney U test and revealed a significantly high uric acid (p<0.001) and low calcium levels (p<0.001) in DPN patients compared to controls. The NLR was significantly high in DPN group {2.62 (2.3-3.1)} compared to that {1.9 (1.6-2.4)} in non-DPN group (p<0.001). Conclusion: Monitoring the simple biomarkers routinely in diabetic patients may give an early signal to prevent DPN and thus better management of the patients.

The Influence Of Spa Therapy And Diabetic Foot Exercise On Diabetic Peripheral Neuropathy Patients

Diabetic peripheral neuropathy patients with decreasing in foot sensation will impact on diabetic ulcers.� This study aims to explore the effect of combination between diabetic legs exercise and SPA therapy on foot sensitivity escalation among patients with diabetic peripheral neuropathy. This study used quasi-experimental pretest-posttest design without control group with 17 respondents and recruited by purposive sampling methode. Data were collected from patients with peripheral diabetic neuropathy and had 8 maximum score of foot sensitivity.. Foot sensitivity was measured on the 1st day of intervention and end day of intervention. Wilcoxon test analysis showed significant differences on foot sensitivity with combination of diabetic legs exercise and SPA therapy compare to diabetic legs exercise only (p value &lt; 0.05). It can be inferred that combination of diabetic legs exercise and SPA therapy are more effective to increase legs sensitivity. Therefore, combined effect of those therapies may eventually decrease diabetic ulcers risk.

The feasibility of using high-resolution ultrasonography to assess ulnar nerve in patients with diabetes mellitus.

ObjectiveThe aim of this study was to investigate the usefulness of high-resolution ultrasonography for the diagnosis of polyneuropathy in diabetes mellitus patients by the examination of the ulnar nerves.MethodWe recruited 100 healthy age-matched volunteers (50 women and 50 men) with 200 arms without diabetes or cubital tunnel syndrome as the control group. We assessed the upper limbs of 100 diabetes mellitus patients (45 women and 55 men), 40 of whom had electrophysiologically confirmed diabetic peripheral neuropathy and 60 had no diabetic peripheral neuropathy in the upper limbs. Age, sex, height and weight were recorded and the cross-sectional area of the ulnar nerve was measured at every predetermined site.ResultsThe cross-sectional area of the ulnar nerve was measured at six sites (mid-humerus, inlet of the cubital tunnel, outlet of the cubital tunnel, upon the medial epicondyle, 6 cm upon the wrist crease and Guyon tunnel). The ulnar nerve in two measuring sites (mid-humerus, upon the medial epicondyle) in the control group showed a statistical difference between men and women (p < 0.05). There was no statistical difference in the cross-sectional area in the control group when dominant and non-dominant arms were compared. The cross-sectional area was larger in the diabetic peripheral neuropathy group in three sites (inlet of the cubital tunnel, outlet of the cubital tunnel, Guyon tunnel) compared with those in the control group.ConclusionHigh-resolution ultrasonography may be helpful in the early diagnosis of peripheral neuropathy in diabetic patients.

Diabetic Neuropathy and Gait: A Review.

Diabetic peripheral neuropathy (DPN) is a major sequela of diabetes mellitus and may have a detrimental effect on the gait of people with this complication. DPN causes a disruption in the body’s sensorimotor system and is believed to affect up to 50% of patients with diabetes mellitus, dependent on the duration of diabetes. It has a major effect on morbidity and mortality. The peripheral nervous system controls the complex series of events in gait through somatic and autonomic functions, careful balancing of eccentric and concentric muscle contractions and a reliance on the sensory information received from the plantar surface. In this literature review focussing on kinetics, kinematics and posture during gait in DPN patients, we have identified an intimate link between DPN and abnormalities in gait and demonstrated an increased risk in falls for older patients with diabetes. As such, we have identified a need for further research on the role of gait abnormalities in the development of diabetic foot ulceration and subsequent amputations.

Effectiveness of wax therapy for diabetic peripheral neuropathy: a systematic review based on GRADE system

Objective To evaluate the efficacy of wax therapy for diabetic peripheral neuropathy, in order to provide suggestions for treatment and prevention. Methods Cochrane Library, JBI, PubMed, EMbase, CBM, CNKI, WANFANG DATA, VIP were searched by computer from inception to October, 2016 for randomized control trails in wax therapy for diabetic peripheral neuropathy. Two researchers searched and selected articles independently and the quality was assessed in accordance with Cochrane Manual. The articles were analyzed with Review Manager 5.3, and the evidence quality was assessed with GRADE profiler 3.6.1 software. Results A total of 8 randomized controlled trials were included. The number of literature quality grade A of original research is 3, while the number of literature quality grade B of original research is 4, and the number of literature quality grade C of original research is 1. Meta-analysis showed that the sensory nervus peronaeus conduction velocities improved by wax therapy for diabetic peripheral neuropathy patients, [MD=2.51, 95%CI (1.35, 3.66) , P<0.01]. By the GRADE system grading, the evidence quality is moderate. Conclusions The effect of wax therapy for diabetic peripheral neuropathy can improve the sensory nurve conduction velocities and speed of blood circle, so as to prevent ulcer of diabetic feet. Therefore, the clinical curative effects of the therapy require large-sample and high quality studies to confirm. Key words: Diabetic peripheral neuropathy; Wax therapy; Systematic review; GRADE system

CHARACERISTICS OF DIABETIC PERIPHERAL NEUROPATIC

Introduction: Diabetes Mellitus (DM) for a long time may experience diabetic peripheral neuropathy (DPN). This study aims to determine the characteristics of diabetic peripheral neuropathy. Methodology: descriptive analytic design with cross sectional design used with 35 samples obtained with purposive sampling technique. The sample of the research was diabetic peripheral neuropathy patients with maximum leg sensitivity score 8. Results: The frequency distribution test results showed the average age of respondents 49.5 � 6.7, female gender (68.4%), diabetes mellitus 4.6 � 2, dominant pharmacological treatment of Oral Hypoglycemic Drugs (OHO) (84.1%) and average ABI values 0.85 � 0.05, mean foot sensation score of 8 � 0.8. Discussion: the characteristics of patients with diabetic peripheral neuropathy are very diverse, it is necessary to see the correlation between characteristics with the incidence of diabetic peripheral neuropathy.

Gait alterations in the UAE population with and without diabetic complications using both traditional and entropy measures

Diabetic foot, one of the most common and debilitating manifestations of type 2 diabetes mellitus (T2DM), is the leading cause of worldwide non-traumatic lower extremity amputations. Diabetics who are at risk of ulceration are currently mainly identified by a thorough clinical examination of the feet, which typically does not show clear symptoms during the early stages of disease progression. In this study, we used a non-linear dynamics tool, gait entropy (GaitEN), in addition to traditional linear gait analysis methods, to investigate gait alterations amongst diabetic patients with combinations of three types of T2DM related complications: retinopathy, diabetic peripheral neuropathy (DPN) and nephropathy. Peak plantar pressure (PPP) was not significantly different in the group with DPN as compared to the control group (diabetics with no complications, CONT) in the forefoot region (DPN: mean±SD: 396±69.4kPa, CONT: 409±68.9kPa), although it was significantly lower in the heel region (DPN: mean±SD: 285±43.1.4kPa, CONT: 295±61.8kPa). On the other hand, gait entropy was significantly lower for the DPN compared to CONT group (DPN: 0.95±0.34, CONT: 1.03±0.28, p<0.05). The significant low entropy was maintained when neuropathy was combined with either retinopathy or nephropathy. For the group with all three complications (ALL-C), the entropy was higher than CONT (ALL-C: 1.07±0.26). This may indicate an intrinsic sensorimotor feedback mechanism for the DPN patients to regulate their gait. However, this feedback gets weaker as patients develop multiple complications. Further analysis with longer walking time and different speeds is needed to verify the entropy results.

The association between vitamin D level and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: An update systematic review and meta-analysis

AimRecently, increasing studies have been carried out to explore the association between vitamin D level and the development of diabetic peripheral neuropathy (DPN) in patients with diabetes mellitus (DM). However, because of the shortcoming in study design and sample size, there is still no clear conclusion. We performed this meta-analysis to examine the exact impact of vitamin D deficiency on DPN in type 2 diabetic patients. MethodsVarious databases were searched to identify the potential articles which explored the association between vitamin D level and diabetic peripheral neuropathy in type 2 diabetes. We pooled OR to assess the correlation between vitamin D deficiency and DPN using the random-effects model. The standardized mean difference (SMD) with 95% CI of vitamin D was also calculated to evaluate the vitamin D level between DPN and non DPN in T2DM. ResultsThere was obvious heterogeneity in those included ten studies (I2=94.1%, Cochran Q test P<0.001) using mean and standard deviation (SD) of vitamin D level. In Caucasian, vitamin D level was significantly lower in DPN patients compared with diabetic patients without DPN (SMD=−0.56, I2=16.9%). In Asian, the pooled OR value of vitamin D deficiency was 1.22 (95%CI: 1.17–1.27). Sensitivity analysis showed one study had great influence on this meta-analysis and it still existed after excluded that one. There was no evidence of public bias in meta analysis as showed in Begg test and Egger test. ConclusionThis meta-analysis indicates that vitamin D deficiency is associated with the generation and development of DPN in Caucasian with T2DM, and in Asian, diabetic patients with vitamin D deficiency are 1.22times to suffer from DPN compared with normal vitamin D level. Vitamin D supplementation is urgently needed to prevent the development of DPN in T2DM.

Tumor necrosis factor-\u03b1 is a novel biomarker for peripheral neuropathy in type II diabetes mellitus: a clinical and electrophysiological study

BackgroundTumor necrosis factor-α (TNF-α) is an adipocytokine locally produced by Schwann cells and has a role in nerve regeneration and regulation of apoptosis. The role of TNF-α in the development of diabetic peripheral neuropathy (DPN) is controversial.ObjectiveThe objective of this study was to evaluate TNF-α serum level in a group of type II diabetes mellitus (DM) patients with and without neuropathy in comparison with healthy age-matched control group.DesignThis is a cross-sectional case–control study.SettingsThe study was conducted in outpatient clinics of the diabetes and physical medicine, rheumatology, and rehabilitation departments.PatientsNinety patients diagnosed with type II diabetes were included in the study.Main outcome measuresAll patients were assessed for clinical neuropathy using neuropathy symptom score and neuropathy disability score. All patients underwent nerve conduction studies of both upper and lower limbs. They were divided into two groups: group I with confirmed DPN (n=60) and group II with DM but no peripheral neuropathy (n=30). Serum TNF-α level was measured in all previous DM patients (90 patients) in addition to 48 healthy age-matched controls.ResultsA statistically significant difference was detected between serum TNF-α level in controls and diabetic patients. Similarly, a significant difference was detected between its level in non-DPN patients and confirmed DPN patients, being higher in the latter. A positive significant correlation has been detected between TNF-α level and patients’ age, as well as blood cholesterol level. A positive significant correlation has been found between TNF-α level and both neuropathy symptom score and neuropathy disability score. A significant negative correlation had been detected between TNF-α level and motor amplitudes of both tibial nerves.ConclusionSerum TNF-α level might be a potential biomarker for peripheral neuropathy in type II DM.

(400) Increased keratinocyte Nav subunit expression among painful diabetic peripheral neuropathy patients predicts Lidoderm patch responsiveness

(400) Increased keratinocyte Nav subunit expression among painful diabetic peripheral neuropathy patients predicts Lidoderm patch responsiveness

Assessment of patient medication adherence among the type 2 diabetes mellitus population with peripheral diabetic neuropathy in South India.

ObjectivesThe present study attempted to explore the relationship between non-adherence with medication and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus (DM) in a private hospital located in South India.MethodsA prospective study was carried out from January 2015 to December 2015. This study included 86 type 2 DM patients with diabetic peripheral neuropathy. The patients were followed-up for three months, once a month. Blood samples were taken to test for fasting blood sugar (FBS), postprandial blood sugar (PPBS) and HbA1c. A Morisky scale questionnaire was used to assess patients' medication adherence and a biothesiometer was used to screen the degree to which patients were affected by diabetic peripheral neuropathy. Patient counselling, which focused on the need for maintaining glycaemic control and the importance of medication adherence, was carried out during each follow-up.ResultsOf the 120 screened subjects, 86 patients were included in the present study. A majority (76.7%) were overweight, and 51% had DM for the past 11–15 years. ANOVA was used to compare patients' glycaemic status, peripheral diabetic neuropathy screening and medication adherence in all three follow-up visits, and p < 0.0001 was considered as significant. Significant improvement in medication adherence and reduction of the peripheral diabetic neuropathy severity (p < 0.0001) were observed from patients' first to third visits.ConclusionsPatient education is prudent for improving medication adherence, a result that can potentially promote optimal glycaemic control and can reduce the prevalence of diabetic peripheral neuropathy in patients with DM. Health-care practitioners play a pivotal role in educating the diabetic population about medication adherence.

Evaluating the Measurement Properties of the Self-Assessment of Treatment Version II, Follow-Up Version, in Patients with Painful Diabetic Peripheral Neuropathy.

Background. The Self-Assessment of Treatment version II (SAT II) measures treatment-related improvements in pain and impacts and impressions of treatment in neuropathic pain patients. The measure has baseline and follow-up versions. This study assesses the measurement properties of the SAT II. Methods. Data from 369 painful diabetic peripheral neuropathy (PDPN) patients from a phase III trial assessing capsaicin 8% patch (Qutenza®) efficacy and safety were used in these analyses. Reliability, convergent validity, known-groups validity, and responsiveness (using the Brief Pain Inventory-Diabetic Neuropathy [BPI-DN] and Patient Global Impression of Change [PGIC]) analyses were conducted, and minimally important differences (MID) were estimated. Results. Exploratory factor analysis supported a one-factor solution for the six impact items. The SAT II has good internal consistency (Cronbach's alpha: 0.96) and test-retest reliability (intraclass correlation coefficients: 0.62–0.88). Assessment of convergent validity showed moderate to strong correlations with change in other study endpoints. Scores varied significantly by level of pain intensity and sleep interference (p < 0.05) defined by the BPI-DN. Responsiveness was shown based on the PGIC. MID estimates ranged from 1.2 to 2.4 (pain improvement) and 1.0 to 2.0 (impact scores). Conclusions. The SAT II is a reliable and valid measure for assessing treatment improvement in PDPN patients.

Association between Hemoglobin Levels and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: A Cross-Sectional Study Using Electronic Health Records.

Objective To investigate the relationship between hemoglobin levels and diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM). Methods 1511 patients with T2DM were included in the study. DPN was diagnosed based on symptoms, signs, and laboratory tests. Hemoglobin was defined as both a continuous variable and a quartile category variable. We compared patient characteristics between the no diabetic peripheral neuropathy (NDPN) and DPN groups. Logistic regression was conducted to investigate the association of DPN with hemoglobin in all T2DM patients. Linear regression was also performed to investigate the impact of hemoglobin on the vibrating perception threshold (VPT). Results Compared with the NDPN group, hemoglobin level in the DPN group was significantly lower (118.54 ± 16.91 versus 131.62 ± 18.32 g/L, P < 0.01). The prevalence of DPN increased by 50.1% (95% CI: 42.2–57.0%; P < 0.001) per standard deviation decrease in hemoglobin. Compared to the highest quartile of hemoglobin, the lower quartiles were associated with a significantly increased risk of DPN in the entire T2DM population (all P < 0.01). A per unit decrease in hemoglobin leads to a 0.12 (95% CI: 0.07–0.168) unit increase in VPT after adjustment for possible confounders (P < 0.001). Conclusions Lower hemoglobin levels were associated with increased prevalence of DPN and higher VPT.

Evaluation of Peripheral Arterial Disease as a Development Factor of Peripheral Neuropathy in Diabetic Patients

Peripheral arterial disease incidence is getting higher in the last years. This is explained due to higher life expectancy of the population, smoking persistence and the high incidence of obese, hypertension e diabetes. In diabetic patients specifically, cardiovascular disease is one of the main cause of morbimortality and the peripheral arterial disease has a huge importance on it. And as known, one of the principal complications of diabetes is the peripheral neuropathy, which may be more aggressive due to peripheral arterial disease in diabetic patients. That is the background for this paper.

Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the “neurotrophin-MAPK signaling pathway” was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.

Assessment of tibial and common peroneal nerves in diabetic peripheral neuropathy by diffusion tensor imaging: a case control study.

To determine the diagnostic accuracy and interobserver performance of diffusion tensor imaging (DTI) in diabetic peripheral neuropathy (DPN) and detect correlations with electrophysiology. Twelve healthy volunteers (controls) and ten DPN patients were enrolled to undergo MR examinations. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of tibial nerve (TN) and common peroneal nerve (CPN) were measured. Unpaired t test and Levene tests were performed to assess differences between the two groups. Receiver operating characteristic (ROC) analysis was performed for FA and ADC values. Pearson correlation coefficient was used to assess the correlation between DTI and electrophysiology parameters in the patient group. The FA values of TN and CPN in the DPN group were significantly lower and ADC were higher than the control group (p < 0.05). Interobserver agreement was excellent. FA positively correlated and ADC negatively correlated with motor nerve conduction velocity (MCV) (p < 0.05). There were no significant differences between motor nerve conduction amplitude and DTI parameters (p > 0.05). Moderate diagnostic accuracy of DTI was seen in the diagnosis of DPN. DTI demonstrates moderate diagnostic accuracy and excellent interobserver performance in the detection of DPN involving the TN and CPN. There is moderate correlation with MCV. • FA values of TN and CPN are significantly lower in DPN. • ADC values of TN and CPN are significantly higher in DPN. • DTI demonstrates moderate diagnostic accuracy in detection of DPN. • There is excellent interobserver performance in DTI measurements. • Moderate correlation is seen between DTI parameters and MCV.

A Trial-Based Economic Evaluation Comparing Spinal Cord Stimulation With Best Medical Treatment in Painful Diabetic Peripheral Neuropathy.

Painful diabetic peripheral neuropathy is a common complication of diabetes mellitus and the humanistic and economic burden is high. This article presents the cost-effectiveness of SCS in patients suffering from painful diabetic peripheral neuropathy from a societal and health care perspective with a time horizon of 12months.

Diabetic peripheral neuropathy: Correlation between nerve cross-sectional area on ultrasound and clinical features.

To evaluate the correlations of the cross-sectional area (CSA) of peripheral nerves in diabetic peripheral neuropathy (DPN) patients based on ultrasound (US) with clinical and demographic characteristics. A DPN patient group (n= 53) and a matched healthy control group (n= 53) underwent US imaging of the sciatic, tibial and median nerves. The CSAs of these nerves were recorded, and their associations with pain intensity according to the visual analog scale (VAS) score and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale score, diabetes mellitus (DM) duration, body mass index (BMI), HbA1c level and blood glucose levels were evaluated. The CSAs of the examined nerves in diabetic patients were larger than those in healthy individuals (p< 0.05). No correlations were detected between the CSAs of the examined nerves and the parameters of interest (p> 0.05), including the VAS and LANSS pain scale scores (p= 0.32 and p= 0.31, respectively). US is a sensitive diagnostic technique for detecting DPN; however, it does not indicate disease severity.

Urine albumin/creatinine ratio is a significant predictor for incident diabetic peripheral neuropathy in patients with Type 2 Diabetes: 3-year prospective study

Urine albumin/creatinine ratio is a significant predictor for incident diabetic peripheral neuropathy in patients with Type 2 Diabetes: 3-year prospective study